Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina?

Abstract

Age-related macular degeneration (AMD) is associated with a low level of macular carotenoids in the eye retina. Only two carotenoids, namely lutein and zeaxanthin are selectively accumulated in the human eye retina from blood plasma where more than twenty other carotenoids are available. The third carotenoid which is found in the human retina, meso-zeaxanthin is formed directly in the retina from lutein. All these carotenoids, named also macular xanthophylls, play key roles in eye health and retinal disease. Macular xanthophylls are thought to combat light-induced damage mediated by reactive oxygen species by absorbing the most damaging incoming wavelength of light prior to the formation of reactive oxygen species (a function expected of carotenoids in nerve fibers) and by chemically and physically quenching reactive oxygen species once they are formed (a function expected of carotenoids in photoreceptor outer segments). There are two major hypotheses about the precise location of macular xanthophylls in the nerve fiber layer of photoreceptor axons and in photoreceptor outer segments. According to the first, macular xanthophylls transversely incorporate in the lipid-bilayer portion of membranes of the human retina. According to the second, macular xanthophylls are protein-bound by membrane-associated, xanthophyll-binding proteins. In this review we indicate specific properties of macular xanthophylls that could help explain their selective accumulation in the primate retina with special attention paid to xanthophyll-membrane interactions.

Keywords: AMD; Carotenoid; Lipid bilayer; Lutein; Macular xanthophylls; Membrane domain; Zeaxanthin.

Figure 1

Chemical structures of macular xanthophylls: lutein, zeaxanthin, meso-zeaxanthin and two dietary carotenoids: non-polar β-carotene and mono-polar β-cryptoxanthin.

Figure 2

Schematic drawing showing the distribution of macular xanthophylls between the saturated raft domain and the unsaturated bulk domain in membranes of POSs. Rhodopsin is also included to show its co-localization with unsaturated lipids and xanthophylls.

Figure 3

Comparison of the antioxidant activity of the macular xanthophyll, lutein, in raft-domain-containing and homogeneous membranes. Antioxidant activity is expressed as (A) a ratio of the rate of lipid hydroperoxide accumulation in membranes in the absence and presence of 0.1 mol% lutein, as a ratio of the oxygen consumption rate in membrane suspension in the absence and presence of (B) 0.3 mol% and (C) 0.5 mol% lutein, and (D) as a ratio of the MDA-TBA adduct accumulation rate in the absence and presence of 0.5 mol% lutein. Homogeneous membranes were made of dioleoylphospatidylcholine (DOPC) (A, B, and C) and didocosahexaenoylphosphatidylcholine (DHAPC) (D). Raft-domain-containing membranes were made of DOPC/sphingomyelin/cholesterol equimolar mixtre (A, B, and C) and DHAPC/distearoylphosphatidylcholine/cholesterol equimolar mixture (D). For more details see Ref. [74].

Figure 4

Schematic drawing of the location of macular xanthophylls in the lipid bilayer membrane. Monomers and H-aggregate are indicated together with their absorption spectra.

Figure 5

Profiles of the oxygen diffusion-concentration product across the dimyristoylphosphatidylcholine membrane measured at 25°C in the absence (○) and presence (●) of 50 mol% cholesterol (A) and 10 mol% zeaxanthin (B). Measurements in (A) were done using saturation-recovery EPR approach with phospholipid-type spin labels. Measurements in (B) were done using line-broadening EPR approach with stearic acid spin labels (SASLs). Approximate locations of the nitroxide moieties of spin labels are indicated by arrows. The nitroxide attached to C16 may pass through the center of the bilayer and stay in the other leaflet of the membrane. Schematic drawings indicate relative positions of membrane modifiers (cholesterol and zeaxanthin) in the lipid bilayer. Figure was made based on data presented in [52] and [54].

Figure 6

Diagram indicating how the lipid bilayer membrane and its domain structure affect the organization of macular xanthophylls within the membrane and how this xanthophyll organization affects their protective activity in membranes of POSs.